๐ ็ธฝ็ฎ้ ๏ฝ ๐ ่ฑๆๅๆ๏ผๆฌ็ฏ๏ผ ๏ฝ ๐ ๅฎๆด็ฟป่ญฏ ๏ฝ โญ ็ฒพ่ฏ็ญ่จ
INHERITED AMYLOIDOSES
The genetic bases of primary localized cutaneous amyloidosis have been previously discussed (see above). Additional inherited forms of amyloidยญosis are listed in Tables 47.1 and 47.2, including those associated with autoinflammatory disorders (see Ch. 45).
Familial Amyloidosis, Finnish Type (AGel Amyloidosis)
Patients with the rare Finnish type of familial amyloidosis, which is due to variants in the gene that encodes gelsolin, present with a characteristic triad of corneal lattice dystrophy, cranial neuropathies, and skin findings including cutis laxa-like changes and skin fragility. Interestingly, despite the multisystem nature of the condition, life expectancy does not seem to be affected.
Transthyretin Amyloidosis (ATTRwt/ATTRv Amyloidosis)
There are two forms of transthyretin amyloidosis: (1) ATTRwt which results from deposition of wild-type transthyretin in cardiac tissue and predominantly affects the elderly; and (2) ATTRv (variant transthyretin amyloidosis) that is due to mutations in the transthyretin gene and presents with either neurologic or cardiac dysfunction. The latter represents the commonest inherited form of systemic amyloidosis. The skin is only rarely involved, although cutaneous amyloid deposition occurs early in the disease and thus abdominal fat pad biopsy can be helpful in diagnosis.
Orthotopic liver transplantation represents a therapeutic option for hereditary ATTR amyloidosis and tafamidis meglumine is FDA-approved for treatment of wild-type or hereditary ATTR cardiomyopathy. Tafamidis binds selectively to transthyretin and slows monomer formation, misfolding, and amyloidogenesis. Patisiran, a small interfering RNA (siRNA), and inotersen, an antisense oligonucleotide, are approved therapies for hereditary ATTR polyneuropathy. A preliminary clinical trial utilized gene-editing CRISPR-Cas9 technology to target and significantly reduce production of misshapen transthyretin by the liver.
Table 47.1 Clinical classification of amyloidosis.